Short-Term Effects of Ginkgo biloba Extract on Peripapillary Retinal Blood Flow in Normal Tension Glaucoma

PURPOSE: Based on the vascular theory of glaucoma pathogenesis, we wanted to evaluate the effect of Ginkgo biloba extract (GBE) on peripapillary blood flow in patients with normal tension glaucoma (NTG). METHODS: Thirty patients with NTG were randomly placed in the GBE-treated or control groups. The GBE-treated group received 80 mg GBE orally, twice a day for four weeks, and the control group received a placebo twice a day for four weeks. Complete ocular examinations including visual field, Heidelberg retina flowmeter, and systemic examinations were performed on the first study day and on the day treatment was completed. RESULTS: After GBE treatment, the mean blood flow, volume, and velocity increased at almost all points, and there was a statistically significant increase in blood flow at almost all points, in comparison to the placebo. Blood volume significantly increased only in the superior nasal and superior temporal neuroretinal rim areas. GBE also significantly increased blood velocity in areas of the inferior temporal neuroretinal rim and superior temporal peripapillary area. CONCLUSIONS: GBE administration appears to have desirable effect on ocular blood flow in NTG patients.ope

Identification of C16orf74 as a Marker of Progression in Primary Non-Muscle Invasive Bladder Cancer

PURPOSE: Methylation-induced silencing of PRSS3 has been shown to be significantly associated with invasive bladder cancer, and expression of the C16orf74 gene locus has been shown to correlate positively with PRSS3. The aim of the current study was to evaluate the relationship between C16orf74 expression level and progression in non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: C16orf74 mRNA levels were examined by real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis of 193 tumor specimens from patients with primary NMIBC. Expression data were analyzed in terms of clinical and experimental parameters. Kaplan-Meier curves and multivariate Cox regression models, respectively, were used to determine progression-free survival and to identify independent predictive parameters of progression. RESULTS: Analysis using Kaplan-Meier curves revealed prolonged progression-free survival of high-C16orf74-expressors as compared to low-expressors (p<0.001). Multivariate Cox regression analysis revealed that low C16orf74 mRNA expression levels are a significant risk factor for disease progression in patients with primary NMIBC (HR: 10.042, CI:2.699-37.360, p = 0.001). CONCLUSIONS: Decreased expression of C16orf74 correlates significantly with progression in primary NMIBC. C16orf74 expression level represents a potentially useful marker for predicting progression in primary NMIBC patients

Involvement of mTOR signaling in sphingosylphosphorylcholine-induced hypopigmentation effects

<p>Abstract</p> <p>Background</p> <p>Sphingosylphosphorylcholine (SPC) acts as a potent lipid mediator and signaling molecule in various cell types. In the present study, we investigated the effects of SPC on melanogenesis and SPC-modulated signaling pathways related to melanin synthesis.</p> <p>Methods</p> <p>Melanin production was measured in Mel-Ab cells. A luciferase assay was used to detect transcriptional activity of the MITF promoter. Western blot analysis was performed to examine SPC-induced signaling pathways.</p> <p>Results</p> <p>SPC produced significant hypopigmentation effects in a dose-dependent manner. It was found that SPC induced not only activation of Akt but also stimulation of mTOR, a downstream mediator of the Akt signaling pathway. Moreover, SPC decreased the levels of LC3 II, which is known to be regulated by mTOR. Treatment with the mTOR inhibitor rapamycin eliminated decreases in melanin and LC3 II levels by SPC. Furthermore, we found that the Akt inhibitor LY294002 restored SPC-mediated downregulation of LC3 II and inhibited the activation of mTOR by SPC.</p> <p>Conclusions</p> <p>Our data suggest that the mTOR signaling pathway is involved in SPC-modulated melanin synthesis.</p

Analysis of clinical and genomic profiles of therapy-related myeloid neoplasm in Korea

Background Therapy-related myeloid neoplasm (T-MN) rarely occurs among cancer survivors, and wascharacterized by poor prognosis. T-MN has germline predisposition in a considerable proportion. Here, clinical characteristics and germline/somatic variant profiles in T-MN patients were investigated, and the findings were compared with those of previous studies. Methods A review of medical records, cytogenetic study, targeted sequencing by next-generation sequencing, and survival analysis were performed on 53 patients with T-MN at a single institution in Korea. Results The patients were relatively younger compared to T-MN patients in other studies. Our T-MN patients showed ahigh frequency of complex karyotypes, −5/del(5q), and −7/del(7q), which was similar to the Japanese study group but higher than the Australian study group. The most common primary disease was non-Hodgkin lymphoma, followed by breast cancer. The detailed distributions of primary diseases were different across study groups. Seven patients (13.2%) harbored deleterious presumed/potential germline variants in cancer predisposition genes (CPG) such as BRIP1, CEBPA, DDX41, FANCM, NBN, NF1, and RUNX1. In the somatic variant profile, TP53 was the most frequently mutated gene, which was consistent with the previous studies about T-MN. However, the somatic variant frequency in our study group was lower than in other studies. Adverse factors for overall survival were male sex, older age, history of previous radiotherapy, previous longer cytotoxic therapy, and −5/del(5q). Conclusion The findings of our study corroborate important information about T-MN patients. As well as a considerable predisposition to CPG, the clinical characteristics and somatic variant profile showed distinctive patterns. Germline variant testing should be recommended for T-MN patients. If the T-MN patients harbor pathogenic germline variants, the family members for stem cell donation should be screened for carrier status through germline variant testing to avoid donor-derived myeloid neoplasm. For the prediction of the prognosis in T-MN patients, sex, age, past treatment history, and cytogenetic findings can be considered.This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean government (MSIT) (NRF-2017R1A2A1A17069780 and NRF-2020R1A3B3079653) and a Grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (Grant No. HR14C0003)

Complete Binocular Blindness as the First Manifestation of HIV-Related Cryptococcal Meningitis

Ocular complications of HIV-related cryptococcal meningitis are reasonably common, but complete binocular blindness as the first manifestation of HIV is extremely rare. A 58-year-old man presented with binocular blindness. He experienced blurred vision for 3 days before the blindness. Mild pleocytosis was present in the cerebrospinal fluid, from which Cryptococcus neoformans was cultured. Serology revealed positivity for HIV antibody. He was treated with antifungal and antiretroviral therapy. This case indicates that HIV-related cryptococcal meningitis should be taken into consideration when determining the cause of unexpected sudden binocular blindness

Phosphatidylcholine induces apoptosis of 3T3-L1 adipocytes

<p>Abstract</p> <p>Background</p> <p>Phosphatidylcholine (PPC) formulation is used for lipolytic injection, even though its mechanism of action is not well understood.</p> <p>Methods</p> <p>The viability of 3T3-L1 pre-adipocytes and differentiated 3T3-L1 cells was measured after treatment of PPC alone, its vehicle sodium deoxycholate (SD), and a PPC formulation. Western blot analysis was performed to examine PPC-induced signaling pathways.</p> <p>Results</p> <p>PPC, SD, and PPC formulation significantly decreased 3T3-L1 cell viability in a concentration-dependent manner. PPC alone was not cytotoxic to CCD-25Sk human fibroblasts at concentrations <1 mg/ml, whereas SD and PPC formulation were cytotoxic. Western blot analysis demonstrated that PPC alone led to the phosphorylation of the stress signaling proteins, such as p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, and activated caspase-9, -8, -3 as well as cleavage of poly(ADP-ribose) polymerase. However, SD did not activate the apoptotic pathways. Instead, SD and PPC formulation induced cell membrane lysis, which may lead to necrosis of cells.</p> <p>Conclusions</p> <p>PPC results in apoptosis of 3T3-L1 cells.</p

Decreased DBC1 Expression Is Associated With Poor Prognosis in Patients With Non-Muscle-Invasive Bladder Cancer

Purpose The deleted in bladder cancer 1 (DBC1) gene is located within chromosome 9 (9q32-33), a chromosomal region that frequently shows loss of heterozygosity in bladder cancer (BC). It is suspected that it acts as a tumor suppressor gene, but its prognostic value remains unclear. The aim of the present study was to investigate the value of DBC1 as a prognostic marker in BC. Materials and Methods The expression of DBC1 was determined by real-time polymerase chain reaction analysis in 344 patients with BC (220 non-muscle-invasive BC [NMIBC] and 124 muscle-invasive BC [MIBC]) and in 34 patients with normal bladder mucosa. The results were compared with clinicopathologic parameters, and the prognostic value of DBC1 was evaluated by Kaplan-Meier analysis and a multivariate Cox regression model. Results: DBC1 expression was significantly decreased in patients with MIBC compared with those diagnosed with NMIBC (p=0.010). Patients with aggressive tumor characteristics had lower DBC1 expression levels in NMIBC (each, p<0.05). By multivariate Cox regression analysis, low DBC1 expression was a predictor of progression to MIBC (hazard ratio, 7.104; p=0.013). Kaplan-Meier estimates revealed a significant difference in tumor recurrence, progression to MIBC, and cancer-specific survival depending on the level of DBC1 expression in NMIBC (log-rank test, each, p<0.05). Conclusions: The expression of DBC1 was associated with tumor aggressiveness, progression to MIBC, and survival in NMIBC. Our results suggest that DBC1 expression can be a useful prognostic marker for patients with NMIBC

Assessment of organic acid and sugar composition in apricot, plumcot, plum, and peach during fruit development

Variation in content of organic acids and soluble sugars, and in physical characteristics was evaluated in apricot (P. armeniaca L. cv. Harcot), plumcot (plum-apricot hybrid, P. salicina ⅹ P. armeniaca L. cv. Harmony), plum (P. salicina Lindl. cv. Formosa), and peach (P. persica L. Batsch cv. Jinmi). The content of organic acids and sugars, as well as parameters of fruit quality (weight, dimensions, firmness, total soluble solids, and total acidity) in Prunus fruits during fruit development were determined. Organic acids, including oxalic acid, quinic acid, malic acid, shikimic acid, citric acid, and quinic acid, sugars, including sucrose, fructose, glucose, and sugar alcohol (sorbitol), were identified and quantified using HPLC. Organic acid mostly increased during the early stages of fruit growth (30 - 60 days after full bloom) and decreased until fruits were fully ripened. In general, plum was the highest in most organic acids compared with the other fruits, while apricot contained the lowest acid content except for citric acid. Sucrose, fructose, and glucose content increased with fruit development, unlike content of sorbitol. Plumcot contained the highest fructose, and peach showed the maximum content of sucrose at full maturation stages. Total soluble solids averaged 17.5, 14.8, 11.9, and 10.6 ºBrix in apricot, plumcot, plum, and peach, respectively, whereas total acidity was 0.9, 1.4, 0.5, and 0.3% in four Prunus cultivars at ripened stages. Shikimic acid was significantly correlated with oxalic acid in apricot, plumcot, and plum, but not in peach. Fructose and glucose were highly correlated in plumcot, plum, and peach.